Respiratory Tract Infections Flashcards
How many droplets does a sneeze produce?
40,000
How many droplets does coughing produce?
3,000
What are the most effective vehicles?
Dried droplet nuclei
Why are dried droplet nuclei such effective vehicles?
They stay airborne for long period of time
1-10 micrometres in diameter
How long do droplets from Influenza (A and B) persist in the environment?
24-72 hours
How long do droplets from SAR-CoV-2 persist in the environment?
up to 3 days
How long do droplets from Bordetella pertussis persist in the environment?
3-5 days
How long do droplets from Mycobacterium tuberculosis persist in the environment?
up to 4 months
What is rhinitis?
Infection of the nose
What is sinusitis?
Inflammation of the sinuses often following a common cold infection
What is pharyngitis?
Infection of the throat
What is laryngitis?
Infection of voice box
What is tracheitis?
Infection of trachea
What is bronchitis?
Infection of bronchi
What is bronchioloitis?
Infection of bronchioles
What is pnemonia?
Infection of alveoli
What is the first line of defence of the respiratory tract?
Mechanisms to remove large incoming particles
What are 4 examples of mechanisms that remove large incoming particles?
Nasal hairs trap particles
Saliva flushing oropharynx
Mucus production throughout respiratory tract
Mucociliary system in trachea and bronchi
What happens to the first line of defence if the epithelial cells are damaged?
It won’t work, secondary bacterial infections can occur
What can damage epithelial cells of the respiratory tract?
bacteria and viruses (e.g. B. pertussis, influenza)
cigarette smoke
pollution
What is the immune response in the alveoli?
Small particles (0.05-3 micrometres) are phagocytosed by alveolar macrophages
What do mucosal secretions produce to provide immune protection?
Antimicrobial substances
- lysozyme (lyses bacteria)
- lactoferrin (iron binding protein that deprives bacteria of the free iron needed for growth)
- secretory IgA (targets specific organisms)
How are specimens collected from the respiratory tract?
Sputum is collected by coughing directly into collection tube or extracted by catheter with suction or during bronchoscopy
Throat or nasopharyngeal swabs
Blood for serological samples
What must be avoided when collecting respiratory samples and why?
Salvia because it is a contaminant due to containing millions of bacteria.
How are respiratory tract infections diagnosed phenotypically?
Through morphology, physiology of organism
- gram stain
- isolation on selective and/or differential media
- biochemical testing: enzyme production, motility, spore formation
- antimicrobial sensitivity
How are respiratory tract infections diagnosed immunologically?
Serology: characterising antibodies
- IgM detectable 4-7 days
- IgG detectable 2-4 weeks
Commercial antibody-based kits to detect pathogens
How are respiratory tract infections diagnosed genotypically?
PCR presence or absence
qPCR amount of pathogen-specific RNA or DNA
High throughput diagnostic chips
Which pathogens adhere to mucosa despite the mucociliary system? (Primary)
Influenza
Rhinovirus
Strep. pneumoniae
M. pneumoniae
Which pathogens interfere with the function of cilia? (Primary)
Bordetella pertussis
M. pneumoniae
Strep. pneumoniae
Which pathogens resist destruction in alveolar macrophages? (Primary)
Legionella
M. tuberculosis
Which pathogens cause local tissue damage? (Primary)
Corynebacterium diphtheriae
Strep. pneumoniae
What are secondary respiratory pathogens?
They are pathogens that infect the host when the host immune barriers are imparied
Which pathogens infect when there is first an initial infection by a respiratory virus?
Staph. aureus
Strep. pneumoniae
Which pathogens infect when there is physiological impairment?
Staph. aureus
Pseudomonas spp.
What disease can cause physiological impairment of the respiratory tract?
Cystic fibrosis
Which pathogens can infect when the host has chronic bronchitis?
Strep. pneumoniae
H. influenzae
Which pathogens can infect when the host is immunocompromised?
A. fumigatus
C. neoformans
What is the most deadly lower respiratory tract infection?
Pneumonia
What is the most common infection-related cause of death in developing countries?
Pneumonia
How many pneumonia deaths per year in children below 5?
935,000
What are the causative agents of pneumonia?
Bacteria
Viruses
Fungi
How do pathogens reach the lower respiratory tract?
Through deep inhalation of aerosols or aspiration of upper respiratory tract flora
What is the main failed defence that leads to pneumonia?
Inhibition of ciliary movement due to tobacco, pollution or prior infection
What are the symptoms of pneumonia?
Runny nose, congestion, headache, fever
Chest pain, cough, production of discoloured sputum, exudate, difficulty breathing
What is lobar pneumonia?
Pneumonia in a distinct region or lobe
What is bronchopneumonia?
Diffuse infection of the lung
What is interstitial pneumonia?
Invasion of the interstitium
What is a lung abcess?
Necrotising pneumonia, destruction of the lung parenchyma
What are the main causes of community acquired pneumonia?
Viral
Strep. pneumoniae
H. influenzae
What are the main causes of nosocomial pneumonia?
Klebsiella pneumoniae
Staph. aureus (MRSA)
Pseudomonas aeruginosa
P. jirovecii
What is atypical pneumonia?
Caused from environmental exposure
What are 3 examples of atypical pneumonia?
Legionella pneumophilia from cooling towers, environment
Brucella spp. Coxiella burnetti from infected animals
Aspergillus fumigatus, Crytococcus spp. from mulch and animal droppings
What percentage of hospitalised patients develop pneumonia?
1%
What is nosocomial pneumonia associated with?
Mechanical ventilation
What is the mortality rate of nosocomial pneumonia?
30-50%
What is the origin of nosocomial pneumonia?
Polymicrobial origin
How is nosocomial pneumonia diagnosed?
Microscopic examination and culture of sputum
X-ray
Bronchoscopy, bronchoalveolar lavage, biopsy
Which part of the respiratory tract does the common cold infect?
The upper respiratory tract
How is the common cold diagnosed?
Through clinical presentation of symptoms
What is the most common cause of the common cold?
Rhinoviruses
What are the symptoms of the common cold?
Rhinorrhoea
Blocked nose
Sore or scratchy throat
Fever
Is there a vaccine for the common cold?
No
What are the main 6 viruses that cause the common cold?
Rhinoviruses Coxsackie virus A Parainfluenza virus Coronaviruses Adenoviruses Echoviruses
What is the pathogenesis of the common cold?
- Limited virulence mechanisms
- Symptoms associated with the immune response releasing cytokines and inflammatory mediators
- Localised inflammation of nasal mucosa leads to rhinorrhoea
- Can predispose a patient to bacterial secondary infection
How is the common cold treated?
rest
fluids
antihistamines
decongestants
How is the common cold diagnosed in a lab?
PCR assays
What type of virus is Rhinovirus?
Single-stranded RNA virus
Enterovirus genus
How many species of Rhinovirus are there?
3
A, B and C
How many serotypes of Rhinovirus are there?
> 165
What are the 3 subtypes of Rhinovirus and what cell receptor do they bind to?
Major (M): intracellular adhesion molecule 1 (ICAM-1)
Minor (m): low-density lipoprotein (LDL)
RV-C: CDHR3
Why is there such diversity in Rhinoviruses?
Because their RNA-dependent RNA polymerase is error-prone
It also undergoes recombination with other Rhinovirus species and other species of the genus Enterovirus
What are anthroponotic respiratory viruses?
They are viruses that infect chimpanzees in Uganda causing severe respiratory disease
Infecting 56 chimps, killing 5
It is closely related to human rhinovirus C45 strains
Chimpanzees are homozygous for what allele?
CDHR3-Y529
Is sinusitis often diagnosed?
No
What is mild sinusitis usually caused by?
viruses
What bacteria can cause sinusitis?
Strep. pneumoniae
H. influenzae
What are the symptoms of sinusitis?
Nasal congestion
Headache
Nasal discharge changes during the course of the illness; may become purulent
What percentage of acute sore throats are caused by viruses?
70%
What are the 3 main viral causes of acute sore throats?
Adenoviruses
Cytomegaloviruses
Epstein-Barr viruses
What are the 2 main bacterial causes of acute sore throats?
Strep. pyogenes
Strep. pneumoniae
What are the symptoms of acute sore throat?
Sore throat
Fever (either low or high grade)
Redness and drainage in the throat
Is a laboratory diagnosis required?
No
What is acute otitis media?
An infection of the air-filled space behind the eardrum (the middle ear).
What demographic is most likely to suffer from acute otitis media?
Young children post cold infection
What are the main causes of acute otitis media?
Nasopharyngeal residents migrating along eustachian tube Strep. pneumoniae H. influenzae M. catarrhalis Strep. pyogenes
What are the symptoms of acute otitis media?
Bulging ear drum
Persistent fluid in the middle ear
Pus
Intense pain
What happens if acute otitis media is not treated adequately?
Chronic discharge
Perforated ear drum
How is S. pyogenes diagnose?
From pharyngeal swab
Rapid antigen test - Ab react to outer carbohydrates of group A streptococci
Culture
What type of bacteria is S. pyogenes?
gram positive cocci, non-motile, non-sporing
Is S. pyogenes fastidious?
Yes, requires sheep blood agar. Shows beta-haemolysis due to haemolysins (streptolysins)
Is S. pyogenes catalase positive or negative?
negative
Is S. pyogenes sensitive to bacitracin?
yes
How is S. pyogenes treated?
Penicillin
What disease does S. pyogenes cause?
Strep throat
What are the virulence factors or S. pyogenes?
Surface M protein
Hyaluronic acid capsule
Lipoteichoic acid: adhesion to pharynx epithelial cells
Extracellular toxins: streptolysin S and O
What encodes pyrogenic exotoxin A (Spe A)?
Lysogenic bacteriophage
What disease do lysogenic bacteriophage (Strep A/S. pyogenes) cause?
Scarlet fever
What are the symptoms of Scarlet fever?
Sore throat headache fever swollen glands in neck sandpaper-like rash
What causes Rheumatic fever?
S. pyogenes strains that contain M proteins which are antigenically similar to human cell surface antigens - ‘rheumatogenic’
What causes damage in rheumatic fever?
Cross-reactive antibodies damage organs
What is rheumatic heart disease?
Disease that arises from multiple infections with different M types of S. pyogenes
What does rheumatic heart disease cause?
myocarditis and pericarditis in children
damage to heart valves
Is there a vaccine for S. pyogenes?
None that are commercially available
target conserved region of M protein
What does the name Corynebacterium diphtheriae mean?
korynee = club for the club shape of the bacterium diphtheria = leather hide
What type of bacteria is Corynebacterium diphtheriae?
aerobic, nonencapsulated, non-spore forming, nonmotile, pleomorphic, gram-positive bacilli
What disease does C. diphtheriae cause?
Diphtheria
What are the symptoms of diphtheria?
Severe sore throat Fever Malaise Swollen lymph nodes Breathing and swallowing problems Pseudomembrane covers pharynx and tonsils
What is a pseudomembrane?
It is a covering of dead cells and bacteria
What gene does the corynebacteriophage carry?
tox gene which produces an exotoxin
How much toxin does 1 corynebacterium produce an hour?
5000 molecules
Where does the diphtheria toxin go in the body?
It is released into the bloodstream and leads to complications in organs including the kidneys and heart
What is the structure of the diphtheria toxin?
It is a single polypeptide with an A unit and a B unit.
What is the cellular process of the diphtheria toxin?
B unit binds to host cell, causing partial cleavage and the toxin-receptor complex in internalised.
The A unit dissociates and moves to the cytosol where it blocks protein synthesis.
When was diphtheria first described?
5th century BC by Hippocrates
When was the diphtheria antitoxin discovered?
In 1890, Emil von Behring demonstrated serum from animals immunised with C. diphtheriae protected susceptible animals from the diphtheria toxin
In what animal is diphtheria antitoxin produced?
Horses
How is diphtheria diagnosed?
Culture of nasal and throat swabs on blood agar
PCR detects toxin producing tox gene
How is diphtheria treated?
Antitoxin: contains neutralising antibodies
Antibiotics: penicillins and macrolides
Is there a vaccine for diphtheria?
Yes, diphtheria toxoid vaccine
Infanrix hexa: diphtheria, tetanus, pertussis, hep B, polio, H. influenzae type B
DTaP vaccine: Diphtheria, Tetanus, acellular Pertussis
What disease does Bordetella pertussis cause?
Whooping cough
What is the incubation period of whooping cough?
2-21 days
What is the initial catarrhal stage of whooping cough?
1-2 weeks
What is the paroxysmal stage of whooping cough?
uncontrollable coughing - “whoops”
paroxysm: convulsive attack
What is the convalescent stage of whooping cough?
recovering from damage to cilia of respiratory tract epithelial cells
What are the consequences of whooping cough in infants?
Necrotising bronchitis
Intra-alveolar haemorrhage
What are the 11 virulence factors of Bordetella pertussis?
- Adhesive structure filamentous haemagglutinin (FHA)
- Fimbriae 2 & 3 (fim2, fim3)
- Pertactin (PRN)
- Tracheal colonisation factor (TCFA)
- Pertussis toxin (PT)
- Adenylate cyclase toxin (ACT)
- Tracheal toxin (TCT)
- Lipopolysaccharide (LPS)
- Dermonecrotic toxin (DNT)
- Serum resistance factor
- Type III secretion system (TTSS)
What does adhesive structure filamentous haemagglutinin do?
Surrounds bacterium like a capsule
- can also be secreted in soluble form and can act as a bridge between bacterium and the epithelial cell
What do fim2 and fim3 do?
adhesion for tracheal epithelial cells
What does pertactin do?
adhesion
What does tracheal colonisation factor do?
cytotoxin
adhesion, predominately, in the trachea
What does pertussis toxin do?
disrupts cellular processes, increases production of mucus
What does adenylate cyclase toxin do?
cytotoxin that inhibits chemotaxis, phagocytosis, bactericidal killing function of neutrophils
What does tracheal toxin do?
directly destroys ciliated cells
Stimulates interleukin-1 causing fever
What does lipopolysaccharide do?
leads to the production of a range of cytokines that inhibit defence functions
What does dermonecrotic toxin do?
dermal necrosis and vasoconstriction
What does serum resistance factor do?
potential adhesins, resistance to complement
What does type III secretion system do?
delivers numerous effector proteins from bacterial cytosol directly into host cells, thus hijacking the intracellular machinery of the infected cells
In what cell type can B. pertussis replicate?
Macrophages, therefore it can also evade destruction
How is whooping cough diagnosed?
Often diagnosed based solely on distinctive symptoms
Culture: nasopharyngeal swab
Serology (IgG or IgA) used after 1 month
PCR
How is whooping cough treated?
Macrolide antibiotics most useful in catarrhal phase
When is whooping cough most contagious?
In the catarrhal and paroxysmal phases
How many cases of whooping cough worldwide in 2014?
24.1 million
How many children under 5 died from whooping cough in 2014?
160,700
How many cases of whooping cough in Australia per year?
12,000
Why is there an increase in cases in Australia over the recent years?
Decrease in immunisation rates
Is there a vaccine for whooping cough?
Yes
Whole cell vaccine: killed B. pertussis cells
Acellular vaccine: toxoid, filamentous haemagglutinin, fimbriae
Infanrix hexa
Boostrix: diphtheria, tenanus, pertussis